This is a variant of a cutaneous T-cell lymphoma.
It likely represents the leukemic phase of mycosis
fungoides. The typical patient is an older adult with generalized erythroderma,
pruritis (itching), and Sezary cells circulating in the peripheral blood.
This Sezary cell is the malignant pleomorphic T cell seen in mycosis fungoides
and has a convoluted nucleus. In the peripheral smear, these cells number
greater than 1.0x10*9/l. Prior to sophisticated molecular techniques such
as flow cytometry, a Sezary prep was performed by concentrating the white
blood cells and doing a morphologic count. However, there are many inflammatory
conditions which may elicit Sezary-like cells in the peripheral smear. In
addition, a morphological appraisal of a peripheral smear slide is not a very
sensitive technique.

A recent proposal for the minimum criteria for the diagnosis includes:

>5% circulating atypical mononuclear cells AND
Evidence of peripheral blood T-cell clone by means of at least one of the
following tests:

The Sezary syndrome is a late and ominous development in mycosis fungoides
and may progress to extensive organ involvement. In general, the higher the
Sezary count, the poorer the prognosis.

Since this is a later stage in the development of mycosis fungoides, the
histopathological features are variable. There is usually irregular epidermal
hyperplasia with spongiosis. Epidermotropism and Pautrier microabscesses may
be present but up to one third of cases may have non-specific findings. In
these cases, the pathologist must correlate the histopathologic findings with
the clinical and molecular studies.

Department of Dermatology, Hamamatsu University School of Medicine,
Japan.

Br J Dermatol 1995 Jul;133(1):6-12 Abstract quote

It has previously been shown that circulating Sezary cells respond
in vitro to superantigenic staphylococcal exotoxins in a manner that
is restricted by their V beta usage.

This study was conducted to examine whether cutaneous colonization
with Staphylococcus aureus influences the activity of the skin lesions
of Sezary syndrome, and whether S. aureus isolated from patients with
Sezary syndrome stimulates circulating Sezary cells in vitro. Two patients
with Sezary syndrome, whose skin was colonized with S. aureus, were
treated with antibacterial agents, and the relation between the severity
of the skin disease and the degree of S. aureus colonization was assessed.
In addition, the patients' peripheral blood mononuclear cells were cultured
in the presence of mitomycin C-treated S. aureus or superantigenic staphylococcal
toxins.

The antibacterial treatment improved the skin disease, and eliminated
S. aureus in both patients. In one patient, 98% of the peripheral blood
mononuclear cells bore V alpha 2V beta 17 of the T-cell receptor, indicative
of the presence of an extremely high percentage of circulating Sezary
cells. The peripheral blood lymphocytes from this patient responded
well in vitro to superantigenic staphylococcal enterotoxin (SE), but
not to SEA or toxic shock syndrome toxin-1, or to mitomycin-treated
S. aureus isolated from the same patient.

Department of Dermatology, University of Texas Medical School, Houston,
USA.

Blood 1997 Jan 1;89(1):32-40 Abstract quote

Forty-two patients with cutaneous T-cell lymphoma, including 31 with
exfoliative erythroderma or Sezary syndrome and 11 with mycosis fungoides,
were studied for the occurrence of staphylococcal infection.

Thirty-two of 42 (76%) had a positive staphylococcal culture from skin
or blood. One half of the patients with positive cultures grew Staphylococcus
aureus. This group included 11 with Sezary syndrome and 5 with rapidly
enlarging mycosis fungoides plaques or tumors. All of the S aureus carried
enterotoxin genes. Surprisingly, 6 of 16 strains were the same toxic
shock toxin-1 (TSST-1)-positive clone, designated electrophoretic type
(ET)-41. Analysis of the T-cell receptor V beta repertoire in 14 CTCL
patients found that only 4 had the expected monoclonal expansion of
a specific V beta gene, whereas 10 had oligoclonal or polyclonal expansion
of several V beta families. All patients with TSST-1+ S aureus had overexpansion
of V beta Z in blood and/or skin lesions.

These studies show that S aureus containing superantigen enterotoxins
are commonly found in patients with CTCL especially individuals with
erythroderma where they could exacerbate and/or perpetuate stimulate
chronic T-cell expansion and cutaneous inflammation. Attention to toxigenic
S aureus in CTCL patients would be expected to improve the quality of
care and outcome of this patient population.

Mycosis fungoides and the Sezary syndrome share common cutaneous histopathologic
features, and this spectrum of malignant disease is referred to here
as cutaneous T-cell lymphoma (CTCL).

A method (LN classification) for describing the histopathologic features
of lymph nodes in CTCL is presented.

In this system, lymph node biopsy specimens are scored according to
the number of atypical lymphoid cells in T-cell-dependent paracortical
zones and the preservation or distortion of the lymph node architecture.
Lymph node architecture is preserved in lymph nodes scored LN1 to LN3,
and these nodes may have coexistent dermatopathic change. LN1 nodes
have single infrequent atypical lymphocytes in paracortical T-cell regions.
LN2 nodes have small clusters of paracortical atypical cells. LN3 nodes
have large clusters of atypical cells. LN4 nodes are partially or totally
effaced by atypical cells. This system was used to classify 96 lymph
node biopsy specimens obtained within six months of the initial diagnosis
of CTCL; no LN1 nodes, 37 LN2, 44 LN3, and 15 LN4 nodes were found.
The LN class was significantly correlated with the extent of skin, blood,
and visceral involvement, as well as with survival. Patients with LN2
lymph nodes have an estimated five-year survival of 70 per cent, while
patients with LN3 and LN4 nodes have estimated five-year survivals of
30 and 15 per cent, respectively. The survival differences between the
LN subgroups were all significant (P less than 0.05).

The LN classification system was clearly shown to be reproducible among
experienced pathologists. The LN system for the histopathologic classification
of lymph nodes in CTCL is of prognostic value and should be used to
assess lymph node biopsies in patients with CTCL.

The dermatopathologic findings in cases of Sézary syndrome (SS) that arise in patients without a previous diagnosis of mycosis fungoides have not been well characterized. We evaluated the histologic findings in skin biopsy specimens from 31 patients with such primary SS and correlated them with clinical and hematologic parameters at the time of biopsy.

The most characteristic histologic finding was the presence of a dermal perivascular lymphoid infiltrate, usually with mild to moderate cytologic atypia and variable numbers of eosinophils; epidermotropism was absent or minimal in 19 cases (61%). Reactive epidermal changes such as spongiosis, parakeratosis, and acanthosis also were present frequently (27 [87%], 17 [55%], 19 [61%] cases, respectively). The number of eosinophils present in skin biopsy specimens correlated with the level of peripheral blood lymphocytosis.

In erythrodermic patients or patients with persistent xerosis and pruritus, it is important to carefully evaluate the degree of lymphocyte atypia in the dermal perivascular infiltrate and correlate with blood flow cytometric findings to diagnose primary SS. Many cases will lack the epidermotropism usually seen in mycosis fungoides.

Peripheral blood involvement has been recognized as an adverse prognostic factor in patients with mycosis fungoides and Sézary syndrome. However, accurate identification and enumeration of the neoplastic cells in these diseases can be challenging.

We assessed the clinical utility of flow cytometric immunophenotypic analysis of T-cell receptor Vbeta expression in 82 mycosis fungoides and 6 Sézary syndrome patients, with an atypical T-cell immunophenotype, or abnormal CD4:CD8 ratio, identified from peripheral blood specimens of 723 patients submitted for routine mycosis fungoides/Sézary syndrome blood staging. To improve detection sensitivity, Vbeta expression was analyzed on gated CD3+CD4+ T cells or T cells with an aberrant immunophenotype, if present. The flow cytometric results were compared with traditional morphologic assessment (n=88) and molecular methods to assess the T-cell receptor gamma or beta genes (n=41 tested in parallel). Flow cytometric immunophenotyping yielded a clonal Vbeta pattern in 60/82 mycosis fungoides and 6/6 Sézary syndrome patients. By contrast, flow cytometric Vbeta was negative in all 10 healthy donors and 18 control patients, showing a specificity of 100% and concordance with molecular testing of 86%. Using flow cytometric Vbeta results instead of morphologic assessment, 12 patients were upstaged from B1 to B2, and 20 patients from B0 to B1 (P<0.0001). The 12 upstaged B2 patients had no morphologic evidence of involvement, but had an aggressive clinical course similar to those staged by traditional morphologic assessment (median survival 27 vs 41 months, log-rank P=0.701). In 30/44 patients with a tumor-associated Vbeta expression, a single Vbeta tube was used to monitor treatment response.

In conclusion, flow cytometric Vbeta analysis is rapid and convenient, can assess T-cell clonality and tumor quantity simultaneously, and is useful both in initial blood staging and monitoring tumor burden during therapy in patients with mycosis fungoides or Sézary syndrome.

The usefulness of CD26 in flow cytometric analysis of peripheral blood in Sézary syndrome.

The loss of CD26 expression was proposed to be a constant feature of circulating Sézary cells by flow cytometric immunophenotyping (FCIP), but the experience with CD26 is limited.

To establish its usefulness, CD26 results were correlated with morphologic, molecular, and immunophenotypic findings. Based on FCIP of 179 samples of peripheral blood, CD26 negativity was found in 59.3% of cases with Sézary syndrome (SS), 33.3% of mycosis fungoides (MF), 14.2% of benign dermatosis (BD), and no control cases.

In diagnostic subgroups of SS based on morphologic, molecular, and immunophenotypic criteria, the percentage of CD26- cases varied from 41.1% to 63.6%.

The specificity of a CD26- result was inferior to that of T-cell antigen loss in differentiating SS from MF and BD. CD26 offers lower diagnostic performance than previously suggested; however, in addition to the findings of major T-cell antigen loss, it could improve sensitivity of FCIP in patients with SS.

Association of change in clinical status and change in the percentage of the CD4+CD26- lymphocyte population in patients with Sezary syndrome.

Department of Dermatology, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.

J Am Acad Dermatol. 2005 Sep;53(3):428-34. Abstract quote

BACKGROUND: Because there are currently many effective therapies available for Sezary syndrome, close monitoring of disease progression is required in order for a clinician to know when to institute or change an intervention. It has been our clinical experience that changes in patients' CD4+CD26- T-cell populations of peripheral blood lymphocytes herald changes in their clinical status.

OBJECTIVE: Our purpose was to evaluate whether a change in patients' CD4+CD26- population of T cells presages a change in their clinical status. We also sought to investigate the association between a change in T-cell populations that are CD4+CD7-, CD8+, CD56+, and the CD4+/CD8+ T-cell ratio and a change in the patient's clinical status.

METHODS: We conducted a retrospective chart review analysis of 21 patients with Sezary syndrome who had flow cytometry, usually including levels of CD4+CD26-, CD4+CD7-, CD8+, CD56+, and CD4+/CD8+ ratios measured at two time periods, 12 weeks apart.

RESULTS: We report two cases in which changes in patients' clinical status were preceded by several weeks by a change in their CD4+CD26- level. We report weak associations between a decreasing CD4+CD26- T-cell population, a decreasing CD4+CD7- population, an increasing CD56+ population, and an improving clinical status. We also report stronger associations between both a decreasing CD8+ population and an increasing CD4+/CD8+ ratio and a worsening clinical status.

LIMITATIONS: The study was limited by the number of patients and the time period over which the study was conducted. In addition, varying configurations of CD4+CD26- T-cell populations were observed that may have limited the utility of this measurement.

CONCLUSIONS: Flow cytometry assays of patients' blood and, in particular, measurement of the CD4+CD26- population of lymphocytes over time may be a valuable tool for monitoring patients with Sezary syndrome. There exist varying configurations of CD26 T lymphocytes that may cause differences in standards for what is considered positive and negative between observers. Further prospective analysis involving larger groups of patients is recommended.

Flow cytometric DNA ploidy analysis of peripheral blood from patients with sezary syndrome: detection of aneuploid neoplastic T cells in the blood is associated with large cell transformation in tissue.

There was no significant difference in blood tumor burden, immunophenotype, or proliferation index between euploid and aneuploid groups or histologic high- and low-grade groups. DNA ploidy study by flow cytometry is important for blood-based diagnosis of SS and detection of minimal residual disease in aneuploid SS after treatment.

Detection of aneuploid neoplastic T cells in peripheral blood samples of patients with CTCL is associated with LCT in skin, lymph node, or other tissues.

Immunoperoxidase

J Am Acad Dermatol 1998;39:554-9.
J Invest Dermatol 1994;102:328-32.

Large expansion of CD4+ CD7- T cells but this can also be found in
the peripheral blood of benign dermatoses

Furthermore, in patients with CD7 expression, the median 5 year survival
was 67% versus 20% in CD7- patients.

Department of Pathology, University of Arkansas for Medical
Sciences, Little Rock, AR, Department of Dermatology, Department of
Pathology, Yale University, New Haven, CT, and Department of Dermatology,
University of Arkansas for Medical Sciences, Little Rock, AR, USA.

J Cutan Pathol. 2003 Aug;30(7):437-442 Abstract quote

BACKGROUND: Sezary syndrome (SS) is an erythrodermic cutaneous T-cell
lymphoma with a leukemic component. Biopsies from these patients may
suggest erythrodermic mycosis fungoides or SS but most often are not
diagnostic. Additional methods are therefore usually needed to diagnose
SS. These include a peripheral blood morphological assessment, flow
cytometry, and gene rearrangement studies. The Cutaneous Lymphoma Study
Group of the European Organization for Research and Treatment of Cancer
has proposed criteria for the diagnosis of SS based on peripheral blood
analysis. These include an increased T-cell count with a CD4/CD8 ratio
of >/=10, in conjunction with evidence of a T-cell clone in the blood
(Willemze et al., Blood 1997; 90: 354-371).

METHODS: We have conducted a study designed to obtain CD4/CD8 ratios
by immunoperoxidase staining of skin biopsies, as opposed to flow cytometry.
Fourteen biopsies from eight patients with SS and 14 control biopsies
were evaluated for CD4/CD8 ratio via double immunostaining.

RESULTS: A CD4/CD8 ratio of >10 : 1 was seen in 85% of SS biopsies
and 43% of controls with horseradish peroxidase used as the CD4 antibody.
With alkaline phosphotase used as the CD4 antibody, 54% of SS biopsies
and 21% of control biopsies exhibited a >10 : 1 ratio. We demonstrate
that double-labeling immunoperoxidase staining with antibodies to CD4
and CD8 on skin biopsies is not specific for SS. By comparing the CD4/CD8
ratios from skin biopsies in Sezary cases with those from biopsies in
inflammatory dermatoses cases, we conclude that flow cytometry remains
the most specific method for determining the CD4/CD8 ratios in patients
with cutaneous eruptions. Although immunohistochemistry would be useful
for laboratories with limited access to flow cytometry, we dismiss such
a use, as CD4/CD8 ratios >/=10 were also found in 21-43% of non-Sezary
cases examined.

CONCLUSIONS: We conclude that a CD4/CD8 ratio >10 : 1 on skin biopsy
is not sufficiently specific to support a diagnosis of SS.

Peripheral blood lymphocytes of patients with SS were analyzed by
two-color flow cytometry using antibodies to the V region of the T cell
receptor (TCR) in combination with an antibody to CD7. In addition,
T cells were analyzed for TCR- gene rearrangement by polymerase chain
reaction (PCR) techniques.

Results: Clonal T-cell expansion was detected in 7 patients with SS
by immunostaining of the TCR V regions. PCR analysis confirmed the presence
of dominant T cell clones. Double-immunostaining revealed that in each
case cells of the clonal V TCR rearrangement homogeneously express the
CD4+CD7– phenotype. Furthermore, CD4+CD7– cells express the CD15s antigen
but lack expression of CD26 and CD49d.

Conclusion: Expansion of clonal T cells strongly correlates with the
expansion of CD4+CD7– T cells in 7 tested patients with SS. This supports
our model that a subset of late differentiated, normal CD4+CD7– memory
T cells may represent the physiologic counterpart of Sézary cells. Monitoring
of circulating T cells with the CD4+CD7–CD15s+CD26–CD49d– phenotype
proved to be useful for the identification of clonal T cells in patients
with SS.

Absence of CD26 Expression Is a Useful Marker for
Diagnosis of T-Cell Lymphoma in Peripheral Blood

In 66 of 69 samples from 28 patients, we identified an abnormal CD26–/dim
T-cell population that was distinct from the variable CD26 expression
seen in normal peripheral blood T cells. This population was CD26– in
23 patients and weakly CD26+ in 5 patients. CD7 was more variably expressed
in MF/SS tumor cells, allowing recognition of a distinct, quantifiable
abnormal T-cell population in only 34 of 69 involved samples. An increased
CD4/CD8 ratio and lower surface expression of CD4 in tumor cells also
helped separate the CD26–/dim atypical population for quantification.
In 35 blood samples from other types of T-cell tumors, tumor cells in
10 of 11 morphologically involved cases showed absent/dim CD26.

Although capable of detecting abnormalities in most cases of MF/SS,
CD7 expression does not provide as clear a separation of the neoplastic
population and can be replaced by CD26 staining in routine peripheral
blood flow cytometric screening of MF/SS patients.

Department of Dermatology, Stanford University School of Medicine,
Stanford, CA 94305, USA.

Arch Dermatol. 2003 Jul;139(7):857-66 Abstract quote

OBJECTIVES: To study and update the clinical characteristics and long-term
outcome of our patients with mycosis fungoides (MF) and Sezary syndrome
(SS), and to identify important clinical factors predictive of survival
and disease progression.

DESIGN: A single-center, retrospective cohort analysis.

SETTING: Academic referral center for cutaneous lymphoma.

PATIENTS: Five hundred twenty-five patients with MF and SS evaluated
and managed at Stanford University Cutaneous Lymphoma Clinic, Stanford,
Calif, from 1958 through 1999.

MAIN OUTCOME MEASURES: We calculated long-term actuarial overall and
disease-specific survivals and disease progression by the Kaplan-Meier
method, and relative risk (RR) for survival calculated from expected
survivals in control populations. RESULTS: The majority of our patients
presented with T1 (30%) or T2 (37%) disease; 18% presented with T3 and
15% with T4 skin involvement. Forty-three percent of deaths were attributable
to MF, primarily in patients with T3 or T4 disease. The patients with
a more advanced T classification and clinical stage had a worse survival
outcome. Except for patients with T1 or stage IA disease, the RR for
death is greater in patients with MF than in a control population (RR,
2.2 in stage IB/IIA disease, 3.9 in stage IIB/III disease, and 12.8
in stage IV disease). Despite similar overall survival in patients with
stage IB or IIA disease, their disease-specific survivals were significantly
different (P =.006). The most significant clinical prognostic factors
in the univariate analysis were patient age, TNM and B classifications,
overall clinical stage groupings, and the presence or absence of extracutaneous
disease. In the multivariate analysis, patient age, T classification,
and the presence of extracutaneous disease were the most important independent
factors. The risk for disease progression to a more advanced TNM or
B classification, worse clinical stage, or death due to MF correlated
with the severity of the initial T classification. The risk for development
of extracutaneous disease also correlated with T classification; none
of these patients had T1 disease when their extracutaneous disease was
detected.

CONCLUSIONS: Patients with MF and SS have varying risks for disease
progression or death. The most important clinical predictive factors
for survival include patient age, T classification, and the presence
of extracutaneous disease. The significant disease-specific survival
differences between different clinical stages validate the usefulness
of the present MF clinical staging system of the National Cancer Institute.

DIABETES MELLITUS

Effect of insulin-dependent diabetes mellitus on response to extracorporeal
photopheresis in patients with Sezary syndrome.

BACKGROUND: Extracorporeal photopheresis (ECP) has become a primary
therapy for selected forms of cutaneous T-cell lymphoma, especially
Sezary syndrome. Variability in response of patients with Sezary syndrome
to ECP has been reported.

OBJECTIVE: Our purpose was to determine whether underlying medical
conditions influence the efficacy of ECP in patients with Sezary syndrome.

METHODS: We retrospectively reviewed the medical records of 55 patients
with Sezary syndrome who received ECP between 1987 and 2000. Efficacy
criteria included decrease in Sezary cell count, erythroderma, lymphadenopathy,
organomegaly, and pruritus.

RESULTS: Thirty-four patients responded well and 10 patients responded
partially to ECP; 11 patients had no response. Nine patients with no
response to ECP had insulin-dependent diabetes mellitus (IDDM). IDDM
was documented in only 2 patients with a good response and in no patients
with a partial response to ECP.

Erythrodermic cutaneous T-cell lymphoma (CTCL) includes patients with
erythrodermic mycosis fungoides who may or may not exhibit blood involvement
and Sezary syndrome and in whom hematological involvement is, by definition,
present at diagnosis.

These patients were stratified into 5 hematologic stages (H0-H4) by
measuring blood tumor burden, and these data were correlated with survival.
The study identified 57 patients: 3 had no evidence of hematologic involvement
(H0), 8 had a peripheral blood T-cell clone detected by polymerase chain
reaction (PCR) analysis of the T-cell receptor gene and less than 5%
Sezary cells on peripheral blood smear (H1), and 14 had either a T-cell
clone detected by Southern blot analysis or PCR positivity with more
than 5% circulating Sezary cells (H2).

Twenty-four patients had absolute Sezary counts of more than 1 x 10(9)
cells per liter (H3), and 8 patients had counts in excess of 10 x 10(9)
cells per liter (H4). The disease-specific death rate was higher with
increasing hematologic stage, after correcting for age at diagnosis.
A univariate analysis of 30 patients with defined lymph node stage found
hematologic stage (P =.045) and lymph node stage (P =.013) but not age
(P =.136) to be poor prognostic indicators of survival. Multivariate
analysis identified only lymph node stage to be prognostically important,
although likelihood ratio tests indicated that hematologic stage provides
additional information (P =.035). Increasing tumor burden in blood and
lymph nodes of patients with erythrodermic CTCL was associated with
a worse prognosis.

The data imply that a hematologic staging system could complement existing
tumor-node-metastasis staging criteria in erythrodermic CTCL.

INTERVENTION: Administration of Caelyx intravenously once every 4 weeks at a dose of 40 mg/m(2).

MAIN OUTCOME MEASURES: The response to treatment was evaluated by clinical evaluation.

RESULTS: At the end of treatment, we observed an objective response (primary end point) in 56% of the patients (14 of 25): 5 complete responses and 9 partial responses. The median overall survival time was 43.7 months. For the 14 patients who experienced an objective response, the median progression-free survival time after the end of treatment was 5 months.

CONCLUSIONS: This prospective study demonstrates the effectiveness of Caelyx in treating CTCL, with an overall response rate of 56% in spite of the high proportion of patients with advanced-stage disease. Responses were observed in 2 subpopulations of patients in which the prognosis is known to be poorer: Sézary syndrome (overall response rate, 60%) and transformed CTCL (overall response rate, 50%). Moreover, this study shows that dose escalation to 40 mg/m(2) does not seem to improve the effectiveness but increases toxic effects (especially hematologic toxic effects) compared with the dose previously tested of 20 mg/m(2).

Department of Dermatology, Division of Special and Environmental
Dermatology, University of Vienna Medical School, Wahringer Gurtel 18-20,
A-1090 Vienna, Austria.

J Am Acad Dermatol 2003 Feb;48(2):220-6 Abstract quote

We describe a patient with therapy-resistant cutaneous T-cell lymphoma,
Sezary syndrome variant, in association with concurrent polyarthritis
and vitiligo, who was successfully treated with extracorporeal photochemotherapy
(ECP).

The combination of Sezary syndrome with seronegative rheumatoid arthritis
is rare. In our patient the T-cell lymphoma was refractory to standard
treatments that included psoralen-UVA, lymph node irradiation, and polychemotherapy.
ECP has been shown to be effective in the treatment of selected cases
of Sezary syndrome. There is a strong suggestion that ECP as a monotherapy
can provide a significant benefit for other T-cell-mediated diseases
including rheumatoid arthritis.

In spite of a disease duration of 10 years, a very low CD8 cell count
(2% of lymphocytes), a very high CD4 cell count (94%), and multiple
unsuccessful chemotherapeutic trials before initiation of ECP, our patient
achieved a long-lasting complete remission of both diseases with normalization
of the CD4+ and CD8+ T-lymphocyte subsets. Concurrent developing vitiligo
was unaffected by ECP.

Circulating CD4+CD7- Lymphocyte Burden and Rapidity of Response: Predictors
of Outcome in the Treatment of Sezary Syndrome and Erythrodermic Mycosis
Fungoides With Extracorporeal Photopheresis.

BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment
for cutaneous T-cell lymphoma. Controversy has arisen regarding its
ability to improve survival rates in Sezary syndrome (SS). We describe
our experience with ECP in the treatment of SS and erythrodermic mycosis
fungoides, with particular emphasis on early predictors of long-term
outcome.

OBSERVATIONS: We included 17 patients (15 with SS and 2 with erythrodermic
mycosis fungoides) who received ECP as initial treatment. Four of these
patients were moribund on presentation (Eastern Cooperative Oncology
Group Performance Status score, 4) and underwent only 1 to 2 cycles
of ECP. The median survival was 56 months for the 11 patients with SS
and an Eastern Cooperative Oncology Group Performance Status score of
less than 4. If all 15 patients with SS are considered, median survival
was 34 months. Response after 5 months of ECP correlated with long-term
survival. A low number (<6.0 x10(3)/ micro L) of circulating CD4(+)CD7(-)
lymphocytes correlated with response after 5 months of ECP.

CONCLUSIONS: Extracorporeal photopheresis is a safe, effective, and
well-tolerated treatment for erythrodermic mycosis fungoides and SS.
Low numbers of CD4(+)CD7(-) cells in the circulation and a positive
response after 5 months of therapy predicted long-term survival. Moribund
patients are much less likely to benefit from ECP.

Objective: Our purpose was to evaluate the cytokine secretion pattern
and cell-mediated cytotoxicity in peripheral blood mononuclear cells
of patients with Sézary syndrome in relation to the presence of the
malignant clone.

Methods: Serial polymerase chain reaction for the T-cell receptor-
or T-cell receptor- gene rearrangement was used to determine the presence
of the malignant clone. Enzyme-linked immunosorbent assays were used
to determine the levels of interleukin 4 and interferon gamma produced
by the peripheral blood mononuclear cells from the patients with Sézary
syndrome.

Results: We demonstrate 3 cases of Sézary syndrome with typically suppressed
cell-mediated cytotoxicity, elevated production of interleukin 4, and
depressed production of interferon gamma by their peripheral blood mononuclear
cells before institution of therapy with biologic response modifier
therapy. In all 3 cases after clinical and molecular remission, we observed
striking immunologic changes, including an increase in levels of natural
killer cell activity and interferon gamma production and decreased production
of interleukin 4.

Conclusions: The observation that the cytokine secretion pattern by
peripheral blood mononuclear cells from 3 patients with Sézary syndrome
normalized with the disappearance of the malignant clone from the peripheral
blood suggests that the malignant T cells account for the aberrant cytokine
production. Moreover, the aberrant cytokine production may be the cause
for suppression of cell-mediated immunity seen in advancing stages of
CTCL.

Combination treatment with extracorporeal photopheresis,
interferon alfa and interleukin-2 in a patient with the Sezary syndrome.

Extracorporeal photopheresis is generally accepted as standard therapy
for the leukaemic and erythrodermic variant of cutaneous T-cell lymphoma,
the Sezary syndrome (SS). Because of the limited efficacy in some patients
with SS, combination therapy is often necessary.

We report a new combination therapy for an intensively treated 62-year-old
woman with advanced SS (T4N1BM1, stage IVb). Previous treatment with
PUVA, retinoids alone and in combination with photopheresis, chlorambucil,
and chemotherapy using cyclophosphamide, doxorubicin, vincristine and
prednisone failed and were associated with significant side-effects.
Six cycles of combination therapy with extracorporeal photopheresis,
low-dose interferon alfa and interleukin-2 resulted in fading of the
erythroderma and in a decrease of Sezary cells in the white blood cell
count. The CD4/CD8 ratio decreased from 66 to 6 and the proportion of
CD4 + CD7 - cells from 47% to 11%. Only mild side-effects such as influenza-like
symptoms, fever and nausea were observed. Two months after this therapy,
the patient developed enlarged lymph nodes without erythroderma, and
died 1 year later from the lymphoma.

Department of Dermatology and the Division of Hematology and Internal
Medicine, Mayo Clinic, Rochester, MN, USA.

Int J Dermatol 2002 Jun;41(6):352-6 Abstract quote

BACKGROUND: 2-Chlorodeoxyadenosine (2-CdA), a purine adenosine analog,
is safe and effective chemotherapy for patients with hairy cell leukemia
and low-grade lymphomas. Adverse effects include neutropenia, lymphocytopenia,
and infectious complications. Our objective was to evaluate the efficacy
of 2-CdA (2-6 seven-day cycles) in the treatment of late-stage, recalcitrant
Sezary syndrome.

METHODS: Retrospective review of medical records of six patients with
Sezary syndrome who had received 2-CdA cycles at Mayo Clinic, Rochester
between March 1995 and March 2000. Variables assessed from the records
included improvement in global appearance, extent of erythroderma, size
of lymph nodes, pruritus, and leukocyte, lymphocyte, and absolute Sezary
cell counts.

RESULTS: Two patients, both with stage III Sezary syndrome, whose previous
treatment consisted of only two modalities, responded well to the treatment,
with moderate to total clearing of erythroderma and pruritus associated
with a significant decrease in Sezary cell counts. The other four patients
had only a partial response (one patient) or no response (three patients)
to 2-CdA. The mortality rate was 50%. All three patients died of Staphylococcus
aureus sepsis. However, only one patient was receiving 2-CdA treatment
when he died. The other two patients died 8 and 9 weeks after the last
2-CdA cycle. This high mortality rate is attributed to infectious complications
after 2-CdA treatment in patients with recalcitrant disease.

CONCLUSION: 2-Chlorodeoxyadenosine shows efficacy in stage III Sezary
syndrome, but it also carries a substantial risk of septic complications
and mortality. It can be used if no other suitable alternatives are
available. Caution should be exercised in all these patients regarding
skin care and avoidance of infections or sepsis.